PMID- 19919843
OWN - NLM
STAT- MEDLINE
DCOM- 20100514
LR  - 20181201
IS  - 1879-016X (Electronic)
IS  - 0163-7258 (Linking)
VI  - 125
IP  - 2
DP  - 2010 Feb
TI  - Impact of genetic and acquired alteration in cytochrome P450 system on 
      pharmacologic and clinical response to clopidogrel.
PG  - 249-59
LID - 10.1016/j.pharmthera.2009.10.008 [doi]
AB  - Dual antiplatelet therapy with aspirin and clopidogrel has been shown to reduce 
      subsequent cardiac events in patients with acute coronary syndrome or coronary 
      artery stenting. Clopidogrel, a thienopyridine, is a prodrug that is transformed 
      in vivo to an active metabolite by the cytochrome P450 (CYP) enzyme system. The 
      genes encoding CYP enzymes are polymorphic. Recent data demonstrated patients 
      carrying a genetic variant of CYP enzymes (e.g. CYP2C19) would have a higher rate 
      of ischemic events than non-carriers due to an attenuation of the pharmacokinetic 
      and pharmacodynamic responses to clopidogrel. Furthermore, concomitant 
      gastrointestinal ulcer prophylaxis with a proton pump inhibitor (PPI) is commonly 
      prescribed to patients because of the increased risk of bleeding with dual 
      antiplatelet therapy. PPIs are extensively metabolized by the cytochrome P450 
      system and have been associated with decreased antiplatelet activity of 
      clopidogrel. In this review, we will discuss the impact of CYP450 enzymes genetic 
      variation and CYP450 pathway drug-drug interactions in pharmacological and 
      clinical response to clopidogrel.
CI  - 2009 Elsevier Inc. All rights reserved.
FAU - Ma, Terry K W
AU  - Ma TK
AD  - Department of Medicine & Therapeutics, Chinese University of Hong Kong, Hong 
      Kong.
FAU - Lam, Yat-Yin
AU  - Lam YY
FAU - Tan, Victoria P
AU  - Tan VP
FAU - Kiernan, Thomas J
AU  - Kiernan TJ
FAU - Yan, Bryan P
AU  - Yan BP
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20091114
PL  - England
TA  - Pharmacol Ther
JT  - Pharmacology & therapeutics
JID - 7905840
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Proton Pump Inhibitors)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - A74586SNO7 (Clopidogrel)
RN  - OM90ZUW7M1 (Ticlopidine)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Aspirin/*pharmacokinetics/therapeutic use
MH  - Calcium Channel Blockers/pharmacology/therapeutic use
MH  - Clopidogrel
MH  - Cytochrome P-450 Enzyme System/*genetics/metabolism
MH  - Drug Interactions
MH  - Drug Resistance
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/therapeutic use
MH  - Platelet Aggregation Inhibitors/*pharmacokinetics/therapeutic use
MH  - Polymorphism, Genetic
MH  - Polypharmacy
MH  - Proton Pump Inhibitors/pharmacology/therapeutic use
MH  - Ticlopidine/*analogs & derivatives/pharmacokinetics/therapeutic use
RF  - 100
EDAT- 2009/11/19 06:00
MHDA- 2010/05/15 06:00
CRDT- 2009/11/19 06:00
PHST- 2009/10/23 00:00 [received]
PHST- 2009/10/26 00:00 [accepted]
PHST- 2009/11/19 06:00 [entrez]
PHST- 2009/11/19 06:00 [pubmed]
PHST- 2010/05/15 06:00 [medline]
AID - S0163-7258(09)00209-5 [pii]
AID - 10.1016/j.pharmthera.2009.10.008 [doi]
PST - ppublish
SO  - Pharmacol Ther. 2010 Feb;125(2):249-59. doi: 10.1016/j.pharmthera.2009.10.008. 
      Epub 2009 Nov 14.